Relaxin-3 and Its Role in Neuroendocrine Function

The hypothalamus plays a key role in the regulation of energy homeostasis and endocrine function. Relaxin-3 is a hypothalamic neuropeptide that belongs to the insulin superfamily of peptides. It is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus and is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role. RXFP3 and RXFP1 are present in the hypothalamic paraventricular nucleus, an area with a well-characterized role in the regulation of energy balance. The paraventricular nucleus also modulates reproductive function by providing inputs to hypothalamic gonadotropin-releasing hormone neurons. The physiological roles for relaxin-3 remain to be established. Evidence for a role of relaxin-3 as a hypothalamic orexigenic peptide will be reviewed, including its effects on the hypothalamo-pituitary-thyroid axis and energy expenditure. Studies pointing towards a putative role of relaxin-3 in the hypothalamic-pituitary-gonadal axis will be discussed. Central endocrine effects of relaxin-3 will be compared to relaxin. We conclude that relaxin-3 may act as a hypothalamic signal to coordinate appetite, thyroid function, and reproductive status. Further studies will be required to determine whether these are physiological roles for relaxin-3 and to determine the receptors involved.